tbuckley/cabot-search huggingface dataset:
Onasemnogene abeparvovec for presymptomatic infants with three copies of SMN2 at risk for spinal muscular atrophy: the Phase III SPR1NT trial
Authors: Kevin A. Strauss, Michelle A. Farrar, Francesco Muntoni, Kayoko Saito, Jerry R. Mendell, Laurent Servais, Hugh J. McMillan, Richard S. Finkel, Kathryn J. Swoboda, Jennifer M. Kwon, Craig M. Zaidman, Claudia A. Chiriboga, Susan T. Iannaccone, Jena M. Krueger, Julie A. Parsons, Perry B. Shieh, Sarah Kavanagh, Melissa Wigderson, Sitra Tauscher-Wisniewski, Bryan E. McGill, Thomas A. Macek
Journal: Nature Medicine (2022)

Most children with biallelic SMN1 deletions and three SMN2 copies develop spinal muscular atrophy (SMA) type 2. SPR1NT ( NCT03505099 ), a Phase III, multicenter, single-arm trial, investigated the efficacy and safety of onasemnogene abeparvovec for presymptomatic children with biallelic SMN1 mutations treated within six postnatal weeks. Of 15 children with three SMN2 copies treated before symptom onset, all stood independently before 24 months (P < 0.0001; 14 within normal developmental window), and 14 walked independently (P < 0.0001; 11 within normal developmental window). All survived without permanent ventilation at 14 months; ten (67%) maintained body weight (≥3rd WHO percentile) without feeding support through 24 months; and none required nutritional or respiratory support. No serious adverse events were considered treatment-related by the investigator. Onasemnogene abeparvovec was effective and well-tolerated for presymptomatic infants at risk of SMA type 2, underscoring the urgency of early identification and intervention.
Perspectives on imaging and immunotherapy: a review series
Authors: Elisabeth GE de Vries, Lawrence H Schwartz
Journal: Journal for ImmunoTherapy of Cancer (2022)

In the latest version of Hallmarks of Cancer, avoiding immune destruction, which had originally been considered an 'emerging hallmark', is now clearly classified as a fundamental characteristic of cancer.[1 2][1] The relevance of this hallmark is becoming increasingly clear. Over the last decade
MAB21L4 Deficiency Drives Squamous Cell Carcinoma via Activation of RET
Authors: Ankit Srivastava, Cristina Tommasi, Dane Sessions, Angela Mah, Tomas Bencomo, Jasmine M. Garcia, Tiffany Jiang, Michael Lee, Joseph Y. Shen, Lek Wei Seow, Audrey Nguyen, Kimal Rajapakshe, Cristian Coarfa, Kenneth Y. Tsai, Vanessa Lopez-Pajares, Carolyn S. Lee
Journal: Cancer Research (2022)

Abstract Epithelial squamous cell carcinomas (SCC) most commonly originate in the skin, where they display disruptions in the normally tightly regulated homeostatic balance between keratinocyte proliferation and terminal differentiation. We performed a transcriptome-wide screen for genes of unknown function that possess inverse expression patterns in differentiating keratinocytes compared with cutaneous SCC (cSCC), leading to the identification of MAB21L4 (C2ORF54) as an enforcer of terminal differentiation that suppresses carcinogenesis. Loss of MAB21L4 in human cSCC organoids increased expression of RET to enable malignant progression. In addition to transcriptional upregulation of RET, deletion of MAB21L4 preempted recruitment of the CacyBP-Siah1 E3 ligase complex to RET and reduced its ubiquitylation. In SCC organoids and in vivo tumor models, genetic disruption of RET or selective inhibition of RET with BLU-667 (pralsetinib) suppressed SCC growth while inducing concomitant differentiation. Overall, loss of MAB21L4 early during SCC development blocks differentiation by increasing RET expression. These results suggest that targeting RET activation is a potential therapeutic strategy for treating SCC. Significance: Downregulation of RET mediated by MAB21L4–CacyBP interaction is required to induce epidermal differentiation and suppress carcinogenesis, suggesting RET inhibition as a potential therapeutic approach in squamous cell carcinoma.
Prevalence of Hearing Loss and Hearing Aid Use Among Adults in France in the CONSTANCES Study
Authors: Quentin Lisan, Marcel Goldberg, Ghizlene Lahlou, Anna Ozguler, Sylvie Lemonnier, Xavier Jouven, Marie Zins, Jean-Philippe Empana
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Although hearing loss is common in the population worldwide, the prevalence of hearing loss and hearing aid use is not known. <h3>Objective</h3> To estimate the prevalence of hearing loss and hearing aid use in the adult French population. <h3>Design, Setting, and Participants</h3> This cohort study used data from the CONSTANCES cohort, a representative sample of the French population. Volunteers aged 18 to 75 years were recruited at 21 preventive health centers between January 1, 2012, and December 31, 2019. The present study included participants with audiometric data. <h3>Main Outcomes and Measures</h3> The main outcomes were prevalence of hearing loss and disabling hearing loss overall and by sex and age group and prevalence of self-reported hearing aid use among those with disabling hearing loss. Hearing loss was defined as a pure-tone average (PTA) in the better ear of 20 dB or higher, and disabling hearing loss was defined as a PTA in the better ear of 35 dB or higher. <h3>Results</h3> Of 200 870 participants in the CONSTANCES study, 186 460 had full audiometric data and were included in this study (mean [SD] age, 47.1 [13.5] years); 100 330 (53.8%) were female, and 86 130 (46.2%) were male. Of these participants, 24.8% (95% CI, 24.6%-25.0%) had hearing loss and 4.3% (95% CI, 4.2%-4.4%) had disabling hearing loss. The prevalence rates of hearing loss increased from 3.4% (95% CI, 2.8%-3.9%) at age 18 to 25 years to 73.3% (95% CI, 69.5%-77.2%) at age 71 to 75 years among men and from 4.4% (95% CI, 3.9%-5.0%) at age 18 to 25 years to 64.1% (95% CI, 59.7%-68.4%) at age 71 to 75 years among women. The prevalence of disabling hearing loss increased from 0.3% (95% CI, 0.2%-0.4%) among participants aged 18 to 25 years to 23.3% (95% CI, 20.7%-26.0%) among participants aged 71 to 75 years. Among the 8050 participants with disabling hearing loss, 36.8% (95% CI, 35.8%-37.9%) reported using hearing aids, including 56.7% (95% CI, 38.9%-74.4%) aged 18 to 25 years and 32.9% (95% CI, 26.8%-39.2%) aged 71 to 75 years. <h3>Conclusions and Relevance</h3> In this cohort study, hearing loss was prevalent in France, and the prevalence of hearing loss increased with age among both men and women. Hearing aids were underused, particularly among older individuals. These findings suggest that hearing loss prevention and screening in the French population are needed.
Evaluation of the Hybrid Tracer Indocyanine Green–99mTc-Nanocolloid for Sentinel Node Biopsy in Bladder Cancer—A Prospective Pilot Study
Authors: Daphne D.D. Rietbergen, Erik J. van Gennep, Gijs H. KleinJan, Maarten Donswijk, Renato A. Valdés Olmos, Bas W. van Rhijn, Henk G. van der Poel, Fijs W.B. van Leeuwen
Journal: Clinical Nuclear Medicine (2022)

In muscle-invasive bladder cancer (MIBC), lymph node invasion has proven to be an independent predictor of disease recurrence and cancer-specific survival. We evaluated the feasibility of targeting the sentinel node (SN) for biopsy in MIBC patients using the hybrid tracer indocyanine green (ICG)- 99m Tc-nanocolloid for simultaneous radioguidance and fluorescence guidance.Twenty histologically confirmed cN0M0 MIBC patients (mean age, 63.3 years; range, 30-82 years), scheduled for radical cystectomy with SN biopsy and extended pelvic lymph node dissection (ePLND), were prospectively included. Twelve patients were operated on following neoadjuvant chemotherapy. The patients received lymphoscintigraphy as well as SPECT/CT after 4 transurethral injections of ICG- 99m Tc-nanocolloid (mean, 208 MBq; range, 172-229 MBq) around the tumor/scar in the detrusor muscle of the bladder on the day before radical cystectomy. Sentinel node resection was performed under radioguidance and fluorescence guidance.Nineteen patients could be analyzed. On preoperative imaging, SNs could be identified in 10 patients (53%; mean, 1.6 SN/patient), which revealed drainage pathways outside the ePLND in 20% of the patients. Interesting to note is that 2 patients (10%) with preoperative nonvisualization displayed fluorescent and radioactive SNs during surgery. Location of the primary tumor near the left lateral side of the bladder seemed to be a factor for nonvisualization. Nodal harvesting with ePLND varied among patients (mean, 23.3). Histopathology confirmed tumor-positive nodes in 4 (21%) of all patients. In the 2 patients where an SN could be identified, the ePLND specimens were tumor-negative. All patients with tumor-positive nodes had advanced disease (stage III).Sentinel node biopsy in bladder cancer using the hybrid tracer ICG- 99m Tc-nanocolloid is feasible, and preoperative imaging is predictive for the ability to perform SN biopsy in 83% of the patients who displayed an SN. In patients with a successful preoperative SN mapping using lymphoscintigraphy and SPECT/CT, the intraoperative SN guidance and detection were effective, even outside the ePLND area. As such, this study underscores the critical role that preoperative imaging plays in challenging image-guided surgery applications.
Is Biannual Surveillance for Pancreatic Cancer Sufficient in Individuals With Genetic Syndromes or Familial Pancreatic Cancer?
Authors: Yifan Wang, Adeline Cuggia, Yen-I Chen, Josée Parent, Agatha Stanek, Robert E. Denroche, Amy Zhang, Robert C. Grant, Céline Domecq, Bryn Golesworthy, Chaya Shwaartz, Ayelet Borgida, Spring Holter, Julie M. Wilson, George Chong, Grainne M. O’Kane, Jennifer J. Knox, Sandra E. Fischer, Steven Gallinger, Zu-Hua Gao, William D. Foulkes, Kevin A. Waschke, George Zogopoulos
Journal: Journal of the National Comprehensive Cancer Network (2022)

Individuals with a family history of pancreatic adenocarcinoma (PC) or with a germline mutation in a PC susceptibility gene are at increased risk of developing PC. These high-risk individuals (HRIs) may benefit from PC surveillance.A PC surveillance program was developed to evaluate the detection of premalignant lesions and early-stage PCs using biannual imaging and to determine whether locally advanced or metastatic PCs develop despite biannual surveillance. From January 2013 to April 2020, asymptomatic HRIs were enrolled and followed with alternating MRI and endoscopic ultrasound every 6 months.Of 75 HRIs, 43 (57.3%) had a germline mutation in a PC susceptibility gene and 32 (42.7%) had a familial pancreatic cancer (FPC) pedigree. Branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) were identified in 26 individuals (34.7%), but only 2 developed progressive lesions. One patient with Peutz-Jeghers syndrome (PJS) developed locally advanced PC arising from a BD-IPMN. Whole-genome sequencing of this patient's PC and of a second patient with PJS-associated PC from the same kindred revealed biallelic inactivation of STK11 in a KRAS-independent manner. A review of 3,853 patients from 2 PC registries identified an additional patient with PJS-associated PC. All 3 patients with PJS developed advanced PC consistent with the malignant transformation of an underlying BD-IPMN in &lt;6 months. The other surveillance patient with a progressive lesion had FPC and underwent resection of a mixed-type IPMN that harbored polyclonal KRAS mutations.PC surveillance identifies a high prevalence of BD-IPMNs in HRIs. Patients with PJS with BD-IPMNs may be at risk for accelerated malignant transformation.
A methodologic problem and a conceptual issue related to the new 2022 antineutrophil cytoplasmic antibody–related vasculitis criteria sets: comment on criteria sets approved by the American College of Rheumatology Board of Directors and the European Alliance of Associations for Rheumatology Executive Committee
Authors: Hasan Yazici, Yusuf Yazici
Journal: Arthritis & Rheumatology (2022)

Disclosure Forms: Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Immune enhancement in patients with predicted severe acute necrotising pancreatitis: a multicentre double-blind randomised controlled trial
Authors: Lu Ke, Jing Zhou, Wenjian Mao, Tao Chen, Yin Zhu, Xinting Pan, Hong Mei, Vikesh Singh, James Buxbaum, Gordon Doig, Chengjian He, Weili Gu, Weihua Lu, Shumin Tu, Haibin Ni, Guoxiu Zhang, Xiangyang Zhao, Junli Sun, Weiwei Chen, Jingchun Song, Min Shao, Jianfeng Tu, Liang Xia, Wenhua He, Qingyun Zhu, Kang Li, Hongyi Yao, Jingyi Wu, Long Fu, Wendi Jiang, He Zhang, Jiajia Lin, Baiqiang Li, Zhihui Tong, John Windsor, Yuxiu Liu, Weiqin Li, Lu Ke, Jing Zhou, Wenjian Mao, Wendi Jiang, He Zhang, Jiajia Lin, Mingfeng Huang, Longxiang Cao, Mengjie Lu, Yan Chen, Gang Li, Bo Ye, Baiqiang Li, Zhihui Tong, Yuxiu Liu, Weiqin Li, Tao Chen, Fang Shao, Nonghua Lv, Yin Zhu, Liang Xia, Wenhua He, Zhenping Chen, Xinting Pan, Qingyun Zhu, Youdong Wan, Hong Mei, Kang Li, Miao Chen, Chengjian He, Hongyi Yao, Zigui Zhu, Weili Gu, Weihua Lu, Jingyi Wu, Feng Zhou, Shumin Tu, Long Fu, Bing Xue, Haibin Ni, Xiaofei Huang, Dandan Zhou, Guoxiu Zhang, Lening Ren, Dahuan Li, Xiangyang Zhao, Wei Zhao, Xiaomei Chen, Junli Sun, Keke Xin, Weiwei Chen, Qingcheng Xu, Jingchun Song, Qingbo Zeng, Min Shao, Dongsheng Zhao, Jianfeng Tu, Hongguo Yang, Bin Wu, Huaguang Ye, Mingzhi Chen, Yingjie Chen, Mei Yang, Hong Gao, Qiang Li, Lijuan Zhao, Guobing Chen, Yafei Li, Honghai Xia, Dongliang Yang, Shusheng Zhou, Jiyan Lin, Siyao Liu, Donghuang Hong, Songjing Shi, Zuozheng Wang, Weijie Yao, Yi Sun, Kaixiu Qin, Shan Xu, Lei Yu, Feng Guo, Yongjun Lin, Yun Zhou, Qinghai Jiao, Quanxing Feng, Zhiyong Li
Journal: Intensive Care Medicine (2022)
Prevalence of autoimmunity and atopy in US adults with glioblastoma and meningioma
Authors: Quinn T Ostrom, Di Lu, Rong Lu, Matthew C Baker
Journal: Neuro-Oncology (2022)

Journal Article Prevalence of autoimmunity and atopy in US adults with glioblastoma and meningioma Get access Quinn T Ostrom, Quinn T Ostrom Department of Neurosurgery, The Preston Robert Tisch Brain Tumor Center, and Duke Cancer Institute, Duke University School of Medicine, Durham, North Carolina, USA Corresponding Author: Quinn T. Ostrom, PhD, MPH, Department of Neurosurgery, The Preston Robert Tisch Brain Tumor Center, and Duke Cancer Institute, Duke University School of Medicine, DUMC Box 3050, Durham, NC 27710, USA (Quinn.Ostrom@duke.edu). https://orcid.org/0000-0003-3469-7558 Search for other works by this author on: Oxford Academic PubMed Google Scholar Di Lu, Di Lu Quantitative Sciences Unit, Department of Medicine, Stanford University, Palo Alto, California, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Rong Lu, Rong Lu Quantitative Sciences Unit, Department of Medicine, Stanford University, Palo Alto, California, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Matthew C Baker Matthew C Baker Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Palo Alto, California, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, Volume 24, Issue 10, October 2022, Pages 1807–1809, https://doi.org/10.1093/neuonc/noac145 Published: 17 June 2022 Article history Corrected and typeset: 17 June 2022 Published: 17 June 2022
Investigation of airport sewage to detect importation of poliovirus, Poland, 2017 to 2020
Authors: Arleta Krzysztoszek, Beata Gad, Sabine Diedrich, Sindy Böttcher, Magdalena Wieczorek
Journal: Eurosurveillance (2022)

Background Polioviruses are human pathogens which may easily be imported via travellers from endemic areas and countries where oral polio vaccine (OPV) is still routinely used to polio-free countries. Risk of reintroduction strictly depends on polio immunisation coverage. Sustaining a polio-free status requires strategies that allow rapid detection and control of potential poliovirus reintroductions. Aim The aim of this study was to apply environmental surveillance at an international airport in Poland to estimate the probability of poliovirus importation via air transport. Methods Between 2017 and 2020, we collected 142 sewage samples at Warsaw Airport. After sewage concentration, virus was isolated in susceptible cell cultures. Poliovirus isolates were characterised by intratypic differentiation and sequencing. Results Seven samples were positive for polioviruses. All isolates were characterised as Sabin-like polioviruses type 3 (SL-3). No wild or vaccine-derived polioviruses were found. The number of mutations accumulated in most isolates suggested a limited circulation in humans. Only one SL-3 isolate contained seven mutations, which is compatible with more than half a year of circulation. Conclusion Since OPV was withdrawn from the immunisation schedule in Poland in 2016, detection of SL-3 in airport sewage may indicate the events of importation from a region where OPV is still in use. Our study shows that environmental surveillance, including airport sewage investigation, has the capacity to detect emerging polioviruses and monitor potential exposure to poliovirus importation. Poliovirus detection in sewage samples indicates the need for sustaining a high level of polio immunisation coverage in the population.
Immunogenicity and reactogenicity of an inactivated SARS-CoV-2 vaccine (BBV152) in children aged 2–18 years: interim data from an open-label, non-randomised, age de-escalation phase 2/3 study
Authors: Krishna Mohan Vadrevu, Siddharth Reddy, Harsh Jogdand, Brunda Ganneru, Nizam Mirza, Virendra Nath Tripathy, Chandramani Singh, Vasant Khalatkar, Siddaiah Prasanth, Sanjay Rai, Raches Ella, William Blackwelder, Sai Prasad, Krishna Ella
Journal: The Lancet Infectious Diseases (2022)
Life expectancy by county, race, and ethnicity in the USA, 2000–19: a systematic analysis of health disparities
Authors: Laura Dwyer-Lindgren, Parkes Kendrick, Yekaterina O Kelly, Dillon O Sylte, Chris Schmidt, Brigette F Blacker, Farah Daoud, Amal A Abdi, Mathew Baumann, Farah Mouhanna, Ethan Kahn, Simon I Hay, George A Mensah, Anna M Nápoles, Eliseo J Pérez-Stable, Meredith Shiels, Neal Freedman, Elizabeth Arias, Stephanie A George, David M Murray, John WR Phillips, Michael L Spittel, Christopher JL Murray, Ali H Mokdad
Journal: The Lancet (2022)
Environmental risks and sphingolipid signatures in adult asthma and its phenotypic clusters: a multicentre study
Authors: Chao-Chien Wu, Chin-Chou Wang, Wen-Yu Chung, Chau-Chyun Sheu, Yi-Hsin Yang, Ming-Yen Cheng, Ruay-Sheng Lai, Sum-Yee Leung, Chi-Cheng Lin, Yu-Feng Wei, Ching-Hsiung Lin, Sheng-Hao Lin, Jeng-Yuan Hsu, Wei-Chang Huang, Chia-Cheng Tseng, Yung-Fa Lai, Meng-Hsuan Cheng, Huang-Chi Chen, Chih-Jen Yang, Shih-Chang Hsu, Chian-Heng Su, Chien-Jen Wang, Huei-Ju Liu, Hua-Ling Chen, Yuan-Ting Hsu, Chih-Hsing Hung, Chon-Lin Lee, Ming-Shyan Huang, Shau-Ku Huang
Journal: Thorax (2022)

Background Adult asthma is phenotypically heterogeneous with unclear aetiology. We aimed to evaluate the potential contribution of environmental exposure and its ensuing response to asthma and its heterogeneity. Methods Environmental risk was evaluated by assessing the records of National Health Insurance Research Database (NHIRD) and residence-based air pollution (particulate matter with diameter less than 2.5 micrometers (PM 2.5 ) and PM 2.5 -bound polycyclic aromatic hydrocarbons (PAHs)), integrating biomonitoring analysis of environmental pollutants, inflammatory markers and sphingolipid metabolites in case–control populations with mass spectrometry and ELISA. Phenotypic clustering was evaluated by t-distributed stochastic neighbor embedding (t-SNE) integrating 18 clinical and demographic variables. Findings In the NHIRD dataset, modest increase in the relative risk with time-lag effect for emergency (N=209 837) and outpatient visits (N=638 538) was observed with increasing levels of PM 2.5 and PAHs. Biomonitoring analysis revealed a panel of metals and organic pollutants, particularly metal Ni and PAH, posing a significant risk for current asthma (ORs=1.28–3.48) and its severity, correlating with the level of oxidative stress markers, notably Nε-(hexanoyl)-lysine (r=0.108–0.311, p&lt;0.05), but not with the accumulated levels of PM 2.5 exposure. Further, levels of circulating sphingosine-1-phosphate and ceramide-1-phosphate were found to discriminate asthma (p&lt;0.001 and p&lt;0.05, respectively), correlating with the levels of PAH (r=0.196, p&lt;0.01) and metal exposure (r=0.202–0.323, p&lt;0.05), respectively, and both correlating with circulating inflammatory markers (r=0.186–0.427, p&lt;0.01). Analysis of six phenotypic clusters and those cases with comorbid type 2 diabetes mellitus (T2DM) revealed cluster-selective environmental risks and biosignatures. Interpretation These results suggest the potential contribution of environmental factors from multiple sources, their ensuing oxidative stress and sphingolipid remodeling to adult asthma and its phenotypic heterogeneity.
Characterization of oral and gut microbiome and plasma metabolomics in COVID-19 patients after 1-year follow-up
Authors: Guang-Ying Cui, Ben-Chen Rao, Zhao-Hai Zeng, Xue-Mei Wang, Tong Ren, Hai-Yu Wang, Hong Luo, Hong-Yan Ren, Chao Liu, Su-Ying Ding, Jun-Jie Tan, Zhen-Guo Liu, Ya-Wen Zou, Zhi-Gang Ren, Zu-Jiang Yu
Journal: Military Medical Research (2022)

Abstract Background Due to the outbreak and rapid spread of coronavirus disease 2019 (COVID-19), more than 160 million patients have become convalescents worldwide to date. Significant alterations have occurred in the gut and oral microbiome and metabonomics of patients with COVID-19. However, it is unknown whether their characteristics return to normal after the 1-year recovery. Methods We recruited 35 confirmed patients to provide specimens at discharge and one year later, as well as 160 healthy controls. A total of 497 samples were prospectively collected, including 219 tongue-coating, 129 stool and 149 plasma samples. Tongue-coating and stool samples were subjected to 16S rRNA sequencing, and plasma samples were subjected to untargeted metabolomics testing. Results The oral and gut microbiome and metabolomics characteristics of the 1-year convalescents were restored to a large extent but did not completely return to normal. In the recovery process, the microbial diversity gradually increased. Butyric acid-producing microbes and Bifidobacterium gradually increased, whereas lipopolysaccharide-producing microbes gradually decreased. In addition, sphingosine-1-phosphate, which is closely related to the inflammatory factor storm of COVID-19, increased significantly during the recovery process. Moreover, the predictive models established based on the microbiome and metabolites of patients at the time of discharge reached high efficacy in predicting their neutralizing antibody levels one year later. Conclusions This study is the first to characterize the oral and gut microbiome and metabonomics in 1-year convalescents of COVID-19. The key microbiome and metabolites in the process of recovery were identified, and provided new treatment ideas for accelerating recovery. And the predictive models based on the microbiome and metabolomics afford new insights for predicting the recovery situation which benefited affected individuals and healthcare.